Hypertension complicates 5-10% of pregnancies. These pregnancies have increased rates of maternal, fetal, and neonatal morbidity and mortality. Thus, hypertension in pregnancy represents a major public health problem. Rational strategies for the prevention and treatment of pregnancy induced hypertension will require a better understanding of the physical factors and chemical agents that regulate placental blood flow. Current understanding of the etiology of pregnancy induced hypertension indicates that uterine ischemia results in the release of a vasoactive substance from the uterine circulation which acts to increase maternal blood pressure and thus to increase utero-placental blood flow. Conversely, the process which leads to pregnancy induced hypertension is associated with an alteration in the balance of factors which regulate placental blood flow even if uterine ischemia is not the primary event. Studies are proposed to examine in detail one system which is thought to be important in the pathogenesis of pregnancy induced hypertension and in the regulation of uteroplacental blood flow, the renin-angiotensin system. This system which chosen because of extensive literature on the renin- angiotensin system and pregnancy induced hypertension, but the model could readily be adapted to study other agents. A chronically catheterized pregnant rabbit model has been chosen because: 1) there is extensive literature about the renin-angiotensin system during rabbit pregnancy, 2) there is literature which suggests that angiotensin II supports utero- placental blood flow in the rabbit, 3) there are important species differences with respect to autoregulation of placental blood flow and the production of maternal hypertension following uterine ischemia, and 4) the rabbit is large enough to permit uterine vein sampling for the purpose of measuring the production of vasoactive substances and the uterine oxygen consumption as an index of fetal well being in a conscious chronically catheterized animal. Experiments will be done for the following purposes: 1) to confirm or disprove autoregulation of uteroplacental blood flow, 2) to assess effects of long term reduction of uterine perfusion pressure on maternal arterial blood pressure, changes in placental vascular resistance, uterine renin production, uterine oxygen consumption and fetal growth, 3) acute affects of angiotensin II and blockade of the renin-angiotensin system on parameters listed in purpose 2, and 4) interactions between the renin-angiotensin system and other agents thought to be important in placental blood flow, ie prostaglandins.